ASCO GU 2018: Optimal Timing of Post-prostatectomy Radiotherapy For Prostate Cancer With High-risk Pathologic Features: A Multi-institutional Analysis

San Francisco, CA (UroToday.com) The standard of care for high-risk localized prostate cancer remains radical prostatectomy or radiotherapy + ADT. While ongoing studies are re-assessing the utility of neoadjuvant therapy prior radiotherapy or surgery, the standard of care remains unchanged. However, despite the primary modality of definitive therapy, biochemical recurrence in this high-risk population remains high (~50-70%), often necessitating multimodal therapy.

Following RP for high-risk localized prostate cancer, defined as patients with Gleason 8+ disease with positive surgical margins or pT3+ disease, subsequent radiotherapy remains an option for management. In contrast, following definitive radiotherapy, salvage prostatectomy is reserved for selected patients.

In men undergoing RP for high-risk localized disease, there has long been a debate regarding the role of adjuvant XRT (based on pathology alone, independent of post-op PSA) vs. early-salvage XRT (evidence of BCR, PSA < 0.5 or even <0.2 ng/mL). The optimal timing of the XRT remains undecided, with each group of supporters citing both risks of unnecessary XRT (adjuvant XRT) vs. missed opportunity for cure (ESRT).

Of note, this study should be noted to have been awarded a Merit Award. Congratulations to the authors of the study.

In this study, the authors of this multi-institutional endeavor pooled data from 10 academic center. They specifically looked at 1566 consecutive men who had pT2N0M0/R1 or pT3N0M0/R0-1 disease on final RP pathology who either underwent post-prostatectomy ART or ESRT between 1987 to 2013 (26 years). Obviously this spans a long period of time over many institutions with the variability that inherently implies.

Their primary outcomes were post-irradiation freedom from biochemical failure (FFBF), freedom from distant metastases (FFDM), prostate-cancer specific survival (PCSS), and overall survival (OS). From a statistical standpoint, they attempted to overcome selection bias by using propensity score (PS) matching. All outcomes were measured from the date of surgery to address lead time bias.

Prior to propensity matched analysis, there were 371 patients treated with ART (PSA < 0.1 ng/mL or undetectable) and 1195 men treated with ESRT (PSA 0.1-0.5 ng/mL). ESRT patients had lower T-stage, Gleason score, positive margin rate and higher rates of post-op ADT. They also note that half of the ESRT patients received < 66 Gy, which is associated with increased risk of BCR – appropriate dosing may negative the below benefits of ART.

Following propensity score matching of 366 well-matched cohorts, their primary results were as follows:

1) Median follow-up after surgery was 66 vs. 73 months for the ART and ESRT groups, respectively, and baseline characteristics were well-matched
2) ART was associated with higher
• FFBF (12-yr: 69% vs. 43%; log-rank P < 0.0001)
• FFDM (12-yr: 95% vs. 85%; log-rank P = 0.03)
• PCSS (12-yr: 99% vs. 94%; log-rank P = 0.048)
• OS (12-yr: 91% vs. 79%; log-rank P = 0.01)
3) On multivariable analysis for biochemical failure, ART, lower Gleason score, lower T-stage, nodal irradiation, and postoperative androgen deprivation therapy were favorable prognostic features
4) Sensitivity analysis demonstrated that, unless 56% of patients were cured with RP alone, ART remained a significant predictor of reduced biochemical failure – which they report is greater than the estimated 12-yr FFBF of 46% after RP alone .

Based on these results, the authors conclude that ART was associated with reduced biochemical recurrence, distant metastases, and death compared to ESRT for high-risk pts. They do recognized the need for prospective validation, but it is still the largest such study of its kind. Prospective validation is coming in the form of the RADICALS, GETUG-17 and RAVES trials.

Limitations / Discussion Points:

1. In the abstract, though hopefully not in the final manuscript, these is no mention of adverse event rates in both groups.
2. No matter how much PS matching is completed, all biases cannot be removed.

Speaker: William Hwang, MD, PhD

Co-authors: Rahul D. Tendulkar, Andrzej Niemierko, Shree Agrawal, Kevin L. Stephans, Daniel Eidelberg Spratt, Jason W.D. Hearn, Bridget F. Koontz, W. Robert Lee, Jeff M. Michalski, Thomas Michael Pisansky, Stanley L. Liauw, Matthew Abramowitz, Alan Pollack, Drew Moghanaki, Mitchell Anscher, Robert Benjamin Den, Anthony L. Zietman, Andrew J. Stephenson, Jason A Efstathiou

Institution(s): Multi-institutional

Written by: Thenappan Chandrasekar, MD, Clinical Fellow, University of Toronto, Twitter: @tchandra_uromd at the 2018 American Society of Clinical Oncology Genitourinary (ASCO GU) Cancers Symposium, February 8-10, 2018 - San Francisco, CA
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